Myeloid neoplasm with PCM1-JAK2presenting with hepatosplenomegaly

Case 376Magdalena Czader, MD, PhD

Indiana UniversityIndianapolis, IN

Clinical history• 13-year-old Caucasian male with a history of ulcerative colitis

• Presented with progressive hepatosplenomegaly and underwent liver biopsy as a work-up for possible primary sclerosing cholangitis or autoimmune hepatitis

• CBC: WBC 13x109/L with eosinophilia (3.3x109/L)hemoglobin 11.2 g/dLMCV 77 fLRDW 17.3%platelet count of 187x109/L

Liver biopsy

Liver biopsy

Liver biopsy

Bone marrow biopsy

Prominent eosinophilia

Expanded erythroid islands

Hemoglobin A CD117

Loose megakaryocyte clusters

Reticulin stain

CD34

Peripheral blood smear

46,XY,t(8;9)(p22;p24)[21]/Nonclonal[2]/46,XY[2]

Proposed diagnosis

Myeloid neoplasm with PCM1-JAK2

2016 WHO classification:Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2

Provisional entity: Myeloid/lymphoid neoplasms with PCM1-JAK2

PCM1

PCM1-JAK2

JAK2

JH2 PTK domain

JH2 PTK domain

Coiled-coil domains

Pericentriolar Material 1 (PCM1)• Localized in cytoplasmic granules-centriolar satellites

• Recruits proteins necessary for centrosome replication• Microtubule organization• Blocking with antibodies or siRNA leads to disorderly

centrosome organization

SH2

SH2

PCM1-JAK2 rearrangement

Dammermann et al. Dev Cell 2004Bousquet et al. Oncogene 2005Murati et al. Leukemia 2005

JAK2 JAK2JAK2mutations

Decreased autoregulation

Hypersensitivity to growth factor

PV, PMF, ET

PCM1-JAK2

Increased oligo/dimerization

Growth factor independent

CEL, aCML, MDS/MPN-U,

AML, ALL

STAT5

STAT5

TRANSCRIPTION ACTIVATION

Protracted Aggressive

Adopted from Smith & Fan Human Pathol 2008

Other partner genes:ETV6, BCR,SSBP2, PAX5,SEC31A

Diverse presentations of myeloid and lymphoid neoplasms with PCM1-JAK2

MPNPMF, PMF in

transformation, CEL

MDS/MPNaCML, MDS/MPN-U

Acute LeukemiasAML including

erythroleukemia, myeloid sarcoma, B and

T-ALL/LBL*Rare case of T cell lymphoma

Stewart et al. Am J Hematol 1990Reiter et al. Cancer Res 2005Murati et al. Leukemia 2005Patterer et al. Ann Hematol 2013Bain and Ahmad Br J Haematol 2014Song et al. Ann Lab Med 2016

• 35 cases• 30 males• Median age 47 (range 12-75 years)

• CBC:• Variable leukocytosis: 11.8-435x109/L• Left shift• Frequent eosinophilia

Diverse presentations of myeloid and lymphoid neoplasms with PCM1-JAK2

Stewart et al. Am J Hematol 1990Reiter et al. Cancer Res 2005Murati et al. Leukemia 2005Patterer et al. Ann Hematol 2013Bain and Ahmad Br J Haematol 2014Song et al. Ann Lab Med 2016

Common features of myeloid neoplasms with PCM1-JAK2

• Male predominance• Hepatosplenomegaly• Hypercellular bone marrow• Bone marrow fibrosis• Eosinophilia• Prominent erythropoiesis with left shift• Frequent transformation to acute leukemia

• Complete and partial responses to ruxolitinib (rare cases reported)

Stewart et al. Am J Hematol 1990 Bain and Ahmad Br J Haematol 2014Reiter et al. Cancer Res 2005 Lierman et al. Blood 2012Murati et al. Leukemia 2005 Rumi et al. JCO 2013Patterer et al. Ann Hematol 2013 Schwaab et al. Ann Hematol 2015

Panel diagnosis

Myeloid/lymphoid neoplasm with PCM1-JAK2